Gene expression in early and progression phases of autosomal dominant polycystic kidney disease.
Gene expression in early and progression phases of autosomal dominant polycystic kidney disease.
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DOI：
10.1186/1756-0500-1-131
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发表时间：
2008-12-21
影响因子：
1.8
通讯作者：
Li, Hung
中科院分区：
文献类型：
--
作者：
Chen, Wen-Cheng;Tzeng, Yi-Shiuan;Li, Hung
背景技术背景：关于常染色体显性遗传性多囊肾病（ADPKD）中最初囊肿形成和疾病进展所涉及的基因知之甚少;然而，这些知识对于探索这种常见遗传性肾病的治疗途径是必要的。为了揭示ADPKD的遗传决定因素和分子机制，我们分析了来自Pkd 1 L3/L3小鼠的4点时间序列DNA微阵列，以生成疾病进展不同阶段的高分辨率基因表达谱。我们发现，在疾病的初始阶段，与年龄匹配的对照组相比，Pkd 1 L3/L3小鼠肾脏中的特征性基因表达特征不同。出生后第1周，Pkd 1 L3/L3肾已经有一个独特的基因表达模式，从相应的正常controls.CONCLUSION：差异表达的基因，无论是诱导或抑制，在ADPKD是重要的免疫防御，细胞结构和运动，细胞增殖，凋亡和代谢过程，并包括三个途径（Wnt，Notch，和BMP）的成员参与形态发生信号。进一步分析从囊肿形成早期到疾病终末期的基因表达谱，发现了一个可能参与ADPKD发病机制的基因网络。
BACKGROUND: Little is known about the genes involved in the initial cyst formation and disease progression in autosomal dominant polycystic kidney disease (ADPKD); however, such knowledge is necessary to explore therapeutic avenues for this common inherited kidney disease.FINDINGS: To uncover the genetic determinants and molecular mechanisms of ADPKD, we analyzed 4-point time-series DNA microarrays from Pkd1L3/L3 mice to generate high resolution gene expression profiles at different stages of disease progression. We found different characteristic gene expression signatures in the kidneys of Pkd1L3/L3 mice compared to age-matched controls during the initial phase of the disease. By postnatal week 1, the Pkd1L3/L3 kidney already had a distinctive gene expression pattern different from the corresponding normal controls.CONCLUSION: The genes differentially expressed, either induced or repressed, in ADPKD are important in immune defense, cell structure and motility, cellular proliferation, apoptosis and metabolic processes, and include members of three pathways (Wnt, Notch, and BMP) involved in morphogenetic signaling. Further analysis of the gene expression profiles from the early stage of cystogenesis to end stage disease identified a possible gene network involved in the pathogenesis of ADPKD.